Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats

Abstract

Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps.

Myeloid-derived growth factor ameliorates dextran sodium sulfate-induced colitis by regulating macrophage polarization

“…The levels of inflammatory cytokines IL-6, TNF-α and IL-1β were measured using ELISA kits as described [ 36 ]. The serum of mice was obtained by centrifugation of 1500 g and 15 min.…”

Bone Marrow Mesenchymal Stem Cells-derived Exosomes Promote Survival of Random Flaps in Rats through Nrf2-mediated Antioxidative Stress

“…Hypoxiainduced exosomes have stronger effects than normal exosomes 12 . In our previous studies, we found that hypoxia-induced exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) reduced skin flap necrosis by increasing angiogenesis following IR injury 13 . However, the underlying mechanism remains unclear and further research is needed.…”

“…(Guangzhou, China). The cultures of BMSCs as well as isolation and identification of exosomes were conducted as previously described 13 .…”

“…Based on the above evidence, we speculated that BMSCs-Exo could increase angiogenesis. Our previous study showed that BMSCs-Exo can increase angiogenesis in I/R-injured skin flaps to improve survival rates and increase the migration and tubular ability of HUVECs 13 . This study found that blood flow perfusion of random flaps was significantly increased in LSCI.…”

Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia–reperfusion injury via mTOR/ULK1/FUNDC1 pathways

“…Through the binding of surface ligands to target cells and the delivery of their internal contents, exosomes regulate a multitude of biological processes, often mirroring the functional attributes of their cells of origin. Currently, exosomes derived from mesenchymal stem cells have demonstrated therapeutic potential in several diseases [11][12][13], most notably in the context of ischaemia-reperfusion injury [14][15][16]. Intriguingly, exosomes derived from hypoxiapreconditioned BMSCs may carry altered cargos, including varied miRNAs, thus significantly enhancing their biological functionality [17][18][19].…”